On July 17, 2017 the U.S. Food and Drug Administration approved neratinib for extended treatment of early-stage HER2-positive breast cancer following completion of 1 year of adjuvant trastuzumab. According to the manufacturer’s website, neratinib is a tyrosine kinase inhibitor that “irreversibly binds to epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4…showing antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines”.1
The ExteNET trial evaluated 2,480 women with early-stage HER2-positive breast cancer who were within 2 years of having completed trastuzumab therapy. They were randomized to receive either neratinib (n = 1,420) or placebo (n = 1,420) for a total of 1 year. The main outcome focus of the study was invasive disease-free survival, defined as the time between the randomization date to the first occurrence of invasive recurrence, distant recurrence, or death from any cause, within 2 years and 28 days of follow-up.2
After 2 years, for those women receiving neratinib, rate of invasive disease-free
survival was 94.2% versus 91.9% in the placebo group (P = .008). The
recommended dosing is 240 mg (6 tablets) taken once daily with food for a total
of 1 year. The most common toxicity leading to discontinuation in almost 17%
of patients was diarrhea. It is now recommended to begin the patient on prophylactic
loperamide for the first 2 months of therapy with the schedule as follows: loperamide
4 mg TID for weeks 1-2, then BID for weeks 3-8, then as needed.1
Other adverse reactions noted in 40% or less of patients included nausea, vomiting, abdominal pain or distention, decreased appetite and weight loss, rash, and elevation in transaminases.
As this drug now becomes available, I find myself asking a few questions:
How many women will want to take a drug for another year after completing a year of intravenous therapy, which only results in a 3% benefit? Especially when those with hormone-positive disease will likely already be taking anti-hormone therapy such as tamoxifen or an aromatase inhibitor. Perhaps those patients who are deemed to have high-risk disease are the best candidates in this situation.
With the pathway targeting EGFR, how else might this drug be utilized in the future for other tumor types? It’s exciting to think about the possibilities.
Have any of you had experience using this drug, either in clinical trials or just in the past month since its release? I welcome your input and feedback.
1. Nerlynx prescribing information. Puma Biotechnology.
www.nerlynx.com. Last accessed September 7, 2017.
2. FDA Approves Neratinib
for Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer.
The ASCO Post. http://www.ascopost.com/News/57838. Last accessed September 7,